Mesenchymal stem cells secretome: The cornerstone of cell-free regenerative medicine

Abstract

Mesenchymal stem cells (MSCs) are the most frequently used stem cells in clinical trials due to their easy isolation from various adult tissues, their ability of homing to injury sites and their potential to differentiate into multiple cell types. However, the realization that the beneficial effect of MSCs relies mainly on their paracrine action, rather than on their engraftment in the recipient tissue and subsequent differentiation, has opened the way to cell-free therapeutic strategies in regenerative medicine. All the soluble factors and vesicles secreted by MSCs are commonly known as secretome. MSCs secretome has a key role in cell-to-cell communication and has been proven to be an active mediator of immune-modulation and regeneration both in vitro and in vivo. Moreover, the use of secretome has key advantages over cell-based therapies, such as a lower immunogenicity and easy production, handling and storage. Importantly, MSCs can be modulated to alter their secretome composition to better suit specific therapeutic goals, thus, opening a large number of possibilities. Altogether these advantages now place MSCs secretome at the center of an important number of investigations in different clinical contexts, enabling rapid scientific progress in this field.

Keywords: Bone regeneration; Exosomes; Extra-cellular vesicles; Mesenchymal stem cells; Secretome; Soluble factors.

Figure 1

Summary of the various soluble factors secreted by mesenchymal stem cells and their functions. HGF: Hepatocyte growth factor; TGF-β: Transforming growth factor–β; IDO: Indoleamine 2,3-dioxygenase; PGE2: Prostaglandin E2; IL: Interleukin; DCs: Dendritic cells; CCL: CC-chemokine ligand; NKs: Natural killer cells; MSCs: Mesenchymal stem cells; CXCR: C-X-C chemokine receptor type; VEGF: Vascular endothelial growth factor; IGF: Insulin-like growth factor; FGF: Fibroblast growth factor; Nrf2: Nuclear factor erythroid-related factor 2; HIF: Hypoxia-inducible factor; SDF: Stromal cell-derived factor; PDGF: Platelet-derived growth factor; ANG1: Angiogenesis 1; MCP-1: Monocyte chemotactic protein-1; ROS: Reactive oxygen species; hCAP: Human cathelicidin anti-microbial peptide; HO-1: Heme oxygenase; NO: Nitric oxide.